11-126204297-A-C

Variant names:

• chr11-126204297-A-C
• rs2276312
• NM_032795.3:c.828T>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_032795.3(RPUSD4):​c.828T>G​(p.Ser276Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RPUSD4 NM_032795.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.513
• Publications: 22 publications found

Genes affected

RPUSD4 (HGNC:25898): (RNA pseudouridine synthase D4) Enables mitochondrial ribosomal large subunit rRNA binding activity; pseudouridine synthase activity; and tRNA binding activity. Involved in mitochondrial tRNA pseudouridine synthesis and positive regulation of mitochondrial translation. Located in mitochondrion; nucleoplasm; and ribonucleoprotein granule. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP7: Synonymous conserved (PhyloP=-0.513 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPUSD4	NM_032795.3	c.828T>G	p.Ser276Ser	synonymous_variant	Exon 6 of 7	ENST00000298317.9	NP_116184.2
RPUSD4	NM_001363516.2	c.828T>G	p.Ser276Ser	synonymous_variant	Exon 6 of 7		NP_001350445.1
RPUSD4	NM_001144827.2	c.735T>G	p.Ser245Ser	synonymous_variant	Exon 6 of 7		NP_001138299.1
RPUSD4	XM_011543039.3	c.249T>G	p.Ser83Ser	synonymous_variant	Exon 4 of 5		XP_011541341.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPUSD4	ENST00000298317.9	c.828T>G	p.Ser276Ser	synonymous_variant	Exon 6 of 7	1	NM_032795.3	ENSP00000298317.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	4.3
DANN	Benign	0.72
PhyloP100		-0.51
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2276312; hg19: chr11-126074192;